Locally Advanced/Metastatic Solid Tumors
Conditions
Keywords
FIH, Solid Tumors
Brief summary
The purpose of this study is to assess the safety and tolerability of BJ-001, a human IL-15 fusion protein, administered via subcutaneous injections, as a single agent and in combination with pembrolizumab in adult patients with Locally Advanced/Metastatic Solid Tumors
Interventions
DRUGBJ-001
BJ-001 dosed via SC injection as single agent. One cycle is 6 weeks.
DRUGPembrolizumab
BJ-001 dosed via SC injection in combination with Pembrolizumab One cycle is 6 weeks.
Sponsors
PPD Development, LP
Merck Sharp & Dohme LLC
BJ Bioscience, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
no masking is used. All involved know the identity of the intervention assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Phase 1a patients must have locally advanced or metastatic solid tumors, * Phase 1b patients must have locally advanced or metastatic and/or non-resectable head and neck squamous cell carcinoma, cholangiocarcinoma, stomach cancer, melanoma, pancreatic cancer, NSCLC (as high expression of αVβ3, αVβ5, or αVβ6 have been reported for these tumors) * Measurable disease: For Phase 1a patients can have non-measurable or measurable disease. For all other parts: measurable disease defined by RECIST v1.1 is required * For Phase 1a Part 3 and Phase 1b patients (combination treatment) must be refractory or relapsed to anti-PD-1, anti-PD-L1 or anti-CTLA4 checkpoint inhibitors for all tumor types, For Part 1 and Part 2 of Phase 1a (BJ-001 single agent treatment) both checkpoint inhibitor naïve or refractory/relapsed patients will be considered. * Patient who have diagnosis for which treatment with pembrolizumab to be enrolled. Patients previously treated with pembrolizumab and who have progressed are eligible. to be enrolled. * Adequate hematologic function, * Adequate hepatic function, defined by all of the following: * Adequate renal function defined by estimated creatinine clearance ≥ 45 mL/min (Cockcroft and Gault formula * ECOG Performance Status (PS) of 0-2. * No history of any hematopoietic malignancy. * No active or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy).
Exclusion criteria
* Pregnant or nursing females. * Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug. Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives (LHRH antagonists are allowed). * Patients previously treated with an anti PD-1/PD-L1 targeting agent who have had any prior history of immune-mediated pneumonitis, any immune-mediated toxicity of ≥ Grade 3, * Patients with a history of severe allergic or anaphylactic reactions to human mAb therapy or known hypersensitivity. * Patients with a history of pneumonitis, myocarditis, history of Stevens-Johnson syndrome or toxic epidermal necrolysis. * Patients who have undergone a bone marrow transplantation, solid organ transplantation, or stem cell transplant. * Patients with unresolved AEs \> Grade 1 from prior anticancer therapy. * Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment. * Uncontrolled primary central nervous system (CNS) tumors or CNS metastases; based on screening. * Patients with active autoimmune disease or a documented medical history of autoimmune disease managed by replacement therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of adverse events (AEs) and SAE | 90 days after the last dose | To assess the safety and tolerability of BJ-001 as a single agent administered s.c. at escalating dose levels in adults with solid tumors. |
| Severity of AEs in patients with solid tumors enrolled in the study. | From Day 1 of treatment up to 30 days after last dose | To assess the safety and tolerability of s.c. BJ-001 administered at escalating dose levels in combination with Pembrolizumab inhibitor. in adults with solid tumors. |
| Dose limiting toxicities (DLTs) BJ-001 as a single agent | at the end of week 4 after first dose | To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of BJ-001 as a single agent. |
| Dose limiting toxicities (DLTs) BJ-001 in combination with pembrolizumab inhibitor. | at the end of week 4 after first dose | To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of s.c. BJ-001 administered at escalating dose levels in combination with pembrolizumab in adults with solid tumors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of BJ-001 as a single agent and in combination with Pembrolizumab. | 90 days after last dose | The frequency of anti-drug antibodies (ADA) against BJ-001 as a single agent and in combination with Pembrolizumab. |
| Pharmacokinetic (PK) Tmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | 24 weeks | PK parameters (Tmax) following the first dose and the fourth dose |
| Pharmacokinetic (PK) AUC0-τ samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | 24 weeks | PK parameters (AUC0-τ) following the first dose and the fourth dose |
| Pharmacokinetic (PK) Cmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | 24 weeks | PK parameters (Cmax) following the first dose and the fourth dose |
| Pharmacokinetic (PK) Ctrough samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | 24 weeks | PK parameters (Ctrough) following the first dose and the fourth dose |
Countries
United States
Outcome results
None listed